Management of Rheumatoid Arthritis with Inadequate Response to Methotrexate and Leflunomide

Immediate Treatment Strategy

The European League Against Rheumatism (EULAR) guidelines strongly recommend adding a biologic DMARD (TNF inhibitor, abatacept, or tocilizumab) to methotrexate while simultaneously tapering and discontinuing the prednisolone as rapidly as clinically feasible, prioritizing agents that may improve glycemic control 1, 2, 3
Start a biologic DMARD immediately since the patient has failed two conventional synthetic DMARDs (methotrexate and leflunomide) and continues to have active disease requiring ongoing corticosteroids, as recommended by EULAR 1, 2, 4
The EULAR guidelines strongly recommend that biologics (TNF inhibitors, abatacept, or tocilizumab) should be commenced with methotrexate in patients responding insufficiently to methotrexate and/or other conventional DMARD strategies 1, 2, 4
No single biologic agent is preferred over another based on the 2014 EULAR update, as direct comparisons show similar efficacy and safety profiles, according to the EULAR guidelines 4

Begin tapering prednisolone immediately once the biologic is initiated, with the goal of complete discontinuation within 3-6 months, as recommended by EULAR 1, 2
The EULAR guidelines strongly recommend that low-dose glucocorticoids should be tapered as rapidly as clinically feasible 1, 2
A practical taper schedule from 7.5 mg: reduce by 1-2.5 mg every 2-4 weeks as disease activity permits, monitoring closely for flare, according to the EULAR guidelines 1

Assess disease activity every 1-3 months using validated composite measures (DAS28, CDAI, or SDAI) to ensure treat-to-target strategy, as recommended by EULAR 1, 2, 7
Expect initial improvement by 3 months; if no improvement is seen, the therapy must be adjusted, according to the EULAR guidelines 1, 2, 7
Target remission or low disease activity by 6 months; if not achieved, switch to another biologic with a different mechanism of action, as recommended by EULAR 1, 2, 5

If biologic therapy is not immediately available due to insurance or cost barriers, switch to triple therapy: methotrexate + sulfasalazine + hydroxychloroquine, as an alternative strategy 1

Weeks 0-2: Initiate biologic DMARD (TNF inhibitor preferred), continue methotrexate, begin prednisolone taper, as recommended by EULAR 1, 2, 4
Month 3: Assess for initial treatment response; if no improvement, adjust therapy, according to the EULAR guidelines 1, 7
Month 6: Target achievement of remission or low disease activity; prednisolone should be discontinued by this point, as recommended by EULAR 1, 2
If treatment target not achieved by month 6: Switch to a different biologic with alternative mechanism of action (e.g., from TNF inhibitor to abatacept or tocilizumab), according to the EULAR guidelines 1, 2, 4